Zidovudine (AZT, Retrovir) is a common component of combination anti-HIV regimens. Zidovudine was taken as a single drug treatment when there were no other treatments available for HIV. However, single drug therapy is no longer used because it is a weak treatment for HIV and leads to rapid development of drug resistance.

Zidovudine should be taken in combination with at least two other anti-HIV drugs to suppress HIV in the blood to very low levels. However, zidovudine monotherapy is sometimes taken during pregnancy, to avoid the possible side-effects of other anti-HIV drugs, as a way of reducing the risk of HIV being passed on from mother to child.

Zidovudine successfully crosses the blood-brain barrier and is effective against HIV in the brain and the central nervous system. Zidovudine is active against HIV-1 and HIV-2.

Zidovudine was licensed in March 1987 after trials showed that a dose of 1200mg per day reduced opportunistic infections and increased CD4 counts and survival among people with AIDS, when compared to placebo over 24 weeks.1 However, longer-term follow-up of this study failed to show a benefit of zidovudine over placebo.2 Later studies confirmed that the lower dose of 600mg per day resulted in similar anti-HIV effects but with less toxicity.3

Further studies tested zidovudine monotherapy among HIV-positive people without symptoms of AIDS. A 1989 placebo-controlled trial called ACTG 019, which enrolled 1338 asymptomatic patients with CD4 cell counts below 500 cells/mm3, found that in the short-term 500 or 1500mg zidovudine every day delayed progression to severe symptomatic disease or AIDS.4 A separate arm of the study compared the effects of zidovudine or a placebo for people with CD4 cell counts above 500 cells/mm3, finding no clinical benefit of starting zidovudine early, although zidovudine recipients did sustain a higher CD4 count than those given placebo.5 However, a subsequent study concluded that the reduction in quality of life brought about by zidovudine’s side-effects in this study approximately equalled the increase in quality of life associated with the delay in disease progression.6

The largest single study of zidovudine monotherapy in asymptomatic HIV infection, known as Concorde, suggested that there was no advantage in starting zidovudine before symptoms develop in the longer term. Almost 1750 participants were randomly assigned either to start taking 1000mg zidovudine a day in four doses, or to receive a placebo until they developed symptoms or until they chose to switch from trial capsules to open zidovudine because of falling CD4 cell counts. The results showed that after three years there was no detectable difference between immediate versus deferred use of zidovudine in terms of disease progression, development of AIDS or survival, but that the patients treated immediately had more severe side-effects.7

Numerous other studies examined the effect of zidovudine monotherapy at various doses and in patients at various stages of HIV infection throughout the late 1980s and early 1990s.8 9 10 11 12 13 A meta-analysis of 15 of these trials by the HIV Trialists’ Collaborative Group published in 1999 confirmed these controversial findings of the Concorde Study - that zidovudine does not increase a person’s chances of AIDS-free survival in the long-term, although it does reduce rates of disease progression in the short-term. However, these studies revealed that adding another NRTI delayed both disease progression and death, paving the way for combination therapy in the treatment of HIV infection.14


  1. Fischl MA et al. The efficacy of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III / LAV replication, to patients with AIDS or AIDS-related complex: a double-blind placebo-controlled trial. N Engl J Med 317: 185-191, 1987
  2. Fischl MA et al. Prolonged zidovudine therapy in patients with AIDS and advanced AIDS-related complex. JAMA 262: 2405-2410, 1989
  3. Fischl MA et al. A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. N Engl J Med 323: 1009-1014, 1990
  4. Volberding PA et al. Zidovudine in asymptomatic HIV infection: a controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimetre. N Engl J Med 322: 941-949, 1990
  5. Volberding PA et al. A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. N Engl J Med 333: 401-407, 1995
  6. Lederking WR et al. Evaluation of the quality of life associated with zidovudine treatment in asymptomatic human immunodeficiency virus infection. N Engl J Med 330: 738-743, 1994
  7. Concorde Co-ordinating Committee MRC / ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet 343: 871-881, 1994
  8. Cooper DA et al. Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. N Engl J Med 329: 297-303, 1993
  9. Mulder JW et al. Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. AIDS 8: 313-321, 1994
  10. Hamilton JD et al. A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. N Engl J Med 326: 437-443, 1992
  11. Simberkoff MS et al. Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment; report of a Veterans Affairs Cooperative Study. VA Cooperative Study Group on AIDS Treatment. J Acquir Immune Defic Syndr 11: 142-150, 1996
  12. Merigan T et al. Placebo-controlled trial to evaluate zidovudine in treatment of human immunodeficiency virus infection in asymptomatic patients with haemophilia. Blood 78: 900-906, 1991
  13. Gardner LI et al. Size and duration of zidovudine benefit in 1003 HIV-infected patients: US Army, Navy, and Air Force natural history data. Military Consortium for Applied Retroviral Research. J Acquir Immune Defic Syndr Hum Retrovirol 17: 345-353, 1998
  14. HIV Trialists' Collaborative Group. Zidovudine, didanosine, and zalcitabine in the treatment of HIV infection: meta-analyses of the randomised evidence. HIV Trialists' Collaborative Group. Lancet 353: 2014-2025, 1999
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.